The goal of this proposal is to investigate how light and dark regions of the visual scene are processed by ON and OFF visual pathways in the cortex under ambient light levels that are common in daily life. Poor illumination is associated with reduced visual acuity and the lack of outdoor activity has been repeatedly related with increased myopia progression. Additionally, dark-exposure has been proposed as a potential mechanism to increase plasticity in visual cortex to treat amblyopia in patients past the critical period. Much of the important wiring in the visual cortex is done when animals are in the dark (pre eye-opening) including retinotopic mapping and the start of orientation selectivity, which are not dependent on visual experience. Thus ambient illumination is likely to have important implications in human visual health and development. Likewise, work on retinal physiology has shown that mean luminance affects ON and OFF pathways differently, however, few studies have examined its effect on the ON/OFF asymmetries in the visual cortex. Most previous studies found differences in ON and OFF responses between scotopic and photopic levels but assumed that ON/OFF response balanced remained unchanged under photopic and mesopic light. Surprisingly, my preliminary evidence demonstrates pronounced changes in the ON//OFF balance when luminance is reduced from photopic to mesopic light levels in both cortical physiology and human psychophysics. The proposed studies will investigate how ON and OFF visual function changes when the mean luminance of the stimulus is reduced to a range of mesopic light levels that are common in everyday life and study the possible consequences of these changes for visual health. In Aim 1, I will measure changes in the balance of ON and OFF cortical responses in animal models as mean luminance is manipulated. To investigate this, multiple thalamic and cortical neurons will be simultaneously recorded and studied with different stimuli including drifting gratings, flashing spots and natural images under different mesopic light levels. I will use automatic receptive field mapping and peri-stimulus time-histograms to measure receptive field structure and center-surround antagonism in both thalamus and cortex. Next, in Aim 2, I will study the possible consequences of changes in ON/OFF response balance for human vision, both in visual acuity and stimulus salience. The outcomes of the proposed studies will address three questions: how cortical and thalamic circuits process ON and OFF retinal signals when light is reduced to mesopic levels, how human visual perception for dark and light targets is affected under low luminance conditions, and possible implications of long-term changes in ON/OFF cortical responses for human visual disease. These goals follow the mission of the National Eye Institute of pursuing mechanisms of visual pathways that may provide insight into visual disorders.